Thiazolo[4,5‐<i>d</i>]pyrimidines. Part I. synthesis and anti‐human cytomegalovirus (HCMV) activity <i>in vitro</i> of certain alkyl derivatives

Lewis, Arthur F.; Revankar, Ganapathi R.; Fennewald, Susan M.; Rando, Robert F.; Huffman, John H.

doi:10.1002/jhet.5570320230

Cited by 17 publications

(5 citation statements)

References 22 publications

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“…Recently we synthesized a series of derivatives of 5-aminothiazolo [4,5-d]pyrimidine-2,7-dione (7-thia-8-oxoguanine) and assayed them for activity against HCMV in culture (14). Several of these compounds were active against HCMV but had various degrees of in vitro toxicity.…”

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confidence: 99%

Inhibition of human cytomegalovirus in culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring system

Lewis

Drach

Fennewald

et al. 1994

Antimicrob Agents Chemother

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A series of alkyl and alkenyl guanine analogs containing a thiazolo [4,5-d]pyrimidine ring system were prepared by reaction of the appropriate alkyl halide with the sodium salt of the heterocycle. In preliminary antiviral efficacy evaluations against laboratory strains of both human cytomegalovirus (HCMV) and herpes simplex virus types 1 and 2, it was determined that two of the compounds (T70072 and T01132) were more active and less toxic in stationary-phase cell monolayers than were the other derivatives tested. T01132 and T70072, which have 2-pentenyl and 3-methyl-2-butenyl moieties attached to position 3 of the 5-aminothiazolo[4,5-dlpyrimidine-2,7-dione, respectively, were then more extensively evaluated for anti-HCMV activity.The concentrations of T01132 and T70072 required to inhibit HCMV by 50%o in plaque reduction assays were -0.5 and 6.8 ,iM, respectively. These two compounds inhibited the growth of KB, or Vero cells at concentrations of 75 to 150 ,uM, depending upon the cell line. In bone marrow progenitor cells T01132 was slightly less toxic than ganciclovir (DHPG). The 50%o inhibitory concentrations of T01132 against clinical isolates and DHPG-resistant strains of HCMV were approximately the same as those obtained for laboratory strains of HCMV (-0.5 jiM). When tested in combination with DHPG, the resultant antiviral activity was determined to be additive but not synergistic. Experiments performed using variations of the viral multiplicity of infection (MOI) demonstrated that T01132 was more active than DHPG at a low MOI (0.002 or 0.02). However, when a higher MOI (0.2 or 2.0) was used, DHPG was more efficacious than T01132. In experiments in which drug was added at various times post-viral infection, T01132 was most effective when added within the first 24 h post-HCMV infection while DHPG was able to protect cells in this assay system when added up to 48 h postinfection, indicating that T01132 is exerting its antiviral effect on events leading up to and possibly including viral DNA synthesis. The data presented in this report suggest that the antiviral activity of alkenyl-substituted thiazolopyrimidine derivatives may represent a mechanism of action against herpesviruses alternative to that of classical nucleoside analogs such as acyclovir or DHPG.

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confidence: 99%

Inhibition of human cytomegalovirus in culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring system

Lewis

Drach

Fennewald

et al. 1994

Antimicrob Agents Chemother

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“…Thiazolo [4,5-d]pyrimidine derivative 151 revealed in vivo activity towards a broad range of RNA and DNA viruses [114] and also had antitumor and antimetastatic activity [115]. The guanine analogs 152 exhibited potent in vitro activity against human cytomegalovirus (HCMV) [116]. Thiazolo [4,5-d] 2,5-Diaminothiazolo [5,4-d]pyrimidin-7(6H)-one (Compound 159), a thio-isostere of 8-aminoguanine, was established to be a poor inhibitor of purine nucleoside phosphorylase (PNP) [123].…”

Section: Biological Importance Of Thiazolesmentioning

confidence: 99%

Significance of Thiazole-based Heterocycles for Bioactive Systems

Pola¹

2016

Scope of Selective Heterocycles From Organic and Pharmaceutical Perspective

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Monocyclic and Bicyclic aromatic heterocycles such as imidazoles, thiazoles, thiadiazoles, oxazoles, oxadiazoles quinazolines, indoles, benzimidazoles, purines pyrido[4,3-d]pyrimidines, thiazolo[5,4-d]pyrimidines, thiazolo[4,5-d]pyrimidines, oxazolo[5,4-d]pyrimidines and thieno[2,3-d]pyrimidines are renowned pharmacophores in drug discovery. These special structures are well explained and exemplified in chemical compound libraries. In this chapter, several types of thiazole based heterocyclic scaffolds such as monocyclic or bicyclic systems synthesis and their biological activities studies are presented, which are not frequently present in books and reviews. We mention the first importance of synthetic route of various thiazole based compounds and their applications in medicinal chemistry in this chapter.

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“…Thiazolo [4,5-d]pyrimidine derivative 151 revealed in vivo activity towards a broad range of RNA and DNA viruses [114] and also had antitumor and antimetastatic activity [115]. The guanine analogs 152 exhibited potent in vitro activity against human cytomegalovirus (HCMV) [116]. Thiazolo [4,5-d] Thiazolo [4,5-d]pyrimidine derivative 151 revealed in vivo activity towards a broad range of RNA and DNA viruses [114] and also had antitumor and antimetastatic activity [115].…”

Section: Sheme 59 Sch59mentioning

confidence: 99%

“…Thiazolo [4,5-d] Thiazolo [4,5-d]pyrimidine derivative 151 revealed in vivo activity towards a broad range of RNA and DNA viruses [114] and also had antitumor and antimetastatic activity [115]. The guanine analogs 152 exhibited potent in vitro activity against human cytomegalovirus (HCMV) [116]. Thiazolo [4,5-d]pyrimidine-5,7-dione analogs (compound 153) have been described as having potential anti-inflammatory activities, because of TNF inhibition [117].…”

Section: Sheme 59 Sch59mentioning

confidence: 99%

Scope of Selective Heterocycles from Organic and Pharmaceutical Perspective

Varala¹

2016

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Ravi Varala received his PhD from the Indian Institute of Chemical Technology (CSIR), India, and was awarded the degree in 2006. Later on, he moved for postdoctoral research in the FCT University of New Lisbon, Portugal, during 2007Portugal, during -2009. He worked as scientist for a year (2010) in pharmaceutical industry, before joining the present organization -Rajiv Gandhi University of Knowledge Technologies (RGUKT), Basar campus, Telangana. He has been working as faculty member there since 2011 onward. Dr. Varala has served as the head of department of chemistry and R&D Cell for more than 3 years. He also got experience as a visiting scientist in the University of Sao Paulo, Brazil, for a period of 1 year (March 2015-2016) and then resumedhis work in RGUKT. His research interests include catalysis, green chemistry, and organic synthesis. Currently he is guiding two students for doctoral degree. He has collaborations in several state and central universities.

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Thiazolo[4,5‐d]pyrimidines. Part I. synthesis and anti‐human cytomegalovirus (HCMV) activity in vitro of certain alkyl derivatives

Cited by 17 publications

References 22 publications

Inhibition of human cytomegalovirus in culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring system

Inhibition of human cytomegalovirus in culture by alkenyl guanine analogs of the thiazolo[4,5-d]pyrimidine ring system

Significance of Thiazole-based Heterocycles for Bioactive Systems

Scope of Selective Heterocycles from Organic and Pharmaceutical Perspective

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